Interleukin-4 receptor Type I complex (IL-4R Type I)

The Interleukin-4 receptor Type I complex is a heterodimeric signaling assembly composed of the Interleukin-4 receptor alpha (IL-4Rα) subunit and the common gamma chain (γc) [1.1.2, 1.5.1]. It is primarily expressed on hematopoietic cells, including T cells, B cells, and myeloid cells, where it specifically binds the cytokine IL-4 to initiate Type 2 immune responses [1.2.2, 1.2.5]. Upon ligand binding, the complex activates the JAK/STAT signaling pathway, specifically involving JAK1, JAK3, and STAT6, which drives the differentiation of naive T cells into Th2 cells and promotes B cell class switching to IgE [1.2.3, 1.3.2]. This signaling axis is a critical driver of allergic and inflammatory diseases such as asthma and atopic dermatitis, making it a major therapeutic target [1.1.1, 1.3.2]. Drugs like dupilumab inhibit this pathway by binding to the IL-4Rα subunit, thereby blocking the formation of both Type I and Type II receptor complexes [1.3.2, 1.3.4]. Beyond allergy, the Type I complex is also implicated in alternative macrophage activation and has been studied for its role in certain cancers and fibrotic conditions [1.1.2, 1.5.2].

Other names

IL-4R Type IIL-4Rα/γc complexCD124/CD132 complexInterleukin-4 receptor alpha/common gamma chain complexType I IL-4 receptor

The Type I complex is formed by the binding of IL-4 to the IL-4Rα subunit, which then recruits the common gamma chain (γc). This dimerization activates associated Janus kinases (JAK1 and JAK3), leading to the phosphorylation of STAT6 and IRS-2, which mediate downstream gene transcription and cellular responses.